Abstract
Current knowledge of the benefits of nutrition supplements for eye pathologies is based largely on the use of appropriate animal models, together with defined dietary supplementation. Here, C57BL6 mice were subretinally injected with polyethylene glycol (PEG)-400, an established model of retinal degeneration with a dry age-related macular degeneration (AMD)-like phenotype, an eye pathology that lacks treatment. In response to PEG-400, markers of the complement system, angiogenesis, inflammation, gliosis, and macrophage infiltration were upregulated in both retinas and retinal pigment epithelium (RPE)/choroids, whereas dietary supplementation with a mixture based on fatty acids counteracted their upregulation. Major effects include a reduction of inflammation, in both retinas and RPE/choroids, and an inhibition of macrophage infiltration in the choroid, yet not in the retina, suggesting a targeted action through the choroidal vasculature. Histological analysis revealed a thinning of the outer nuclear layer (ONL), together with dysregulation of the epithelium layer in response to PEG-400. In addition, immunohistofluorescence demonstrated Müller cell gliosis and macrophage infiltration into subretinal tissues supporting the molecular findings. Reduced ONL thickness, gliosis, and macrophage infiltration were counteracted by the diet supplement. The present data suggest that fatty acids may represent a useful form of diet supplementation to prevent or limit the progression of dry AMD.
Highlights
Age-related macular degeneration (AMD) is the leading cause of blindness in the world, and its global prevalence is projected at 196 million by the year 2020 increasing to 288 million in 2040 [1].Dry AMD accounts for the majority of AMD cases [2] and is characterized by drusen deposits between the retinal pigment epithelium (RPE) and the choroid
In the biomolecular cascade activated by polyethylene glycol (PEG)-400, mFAG has been found to reduce inflammation and macrophage infiltration, without interfering with the upregulation of the complement system. This is in line with the concept that the complement system is difficult to modulate with small molecules, anti-complement therapies are under investigation for use in AMD [46], in agreement with the findings presented here of increased C3 and C5 in the dry AMD-like mouse model
The results presented here show the first evidence of dietary supplementation efficacy in the PEG-400 mouse model of retinal damage
Summary
Dry AMD accounts for the majority (up to 90%) of AMD cases [2] and is characterized by drusen deposits between the retinal pigment epithelium (RPE) and the choroid. Advanced dry AMD leads to regions of massive RPE death or geographic atrophy (GA). Some patients advance to wet AMD, with impairment of the RPE layer and invasion of the subretinal space by newly-formed choroidal neovascularization (CNV) [3]. In both cases, advanced AMD culminates in the loss of photoreceptor cells, with subsequent severe visual impairment and, blindness
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